Exploring New Combinations in Ovarian Cancer

A phase 2 study is examining Keytruda in combination with two other agents for treatment of ovarian cancer.
With a new phase 2 clinical trial underway, researchers at Roswell Park Cancer Institute are hoping to bring the use of checkpoint inhibitors into the treatment realm for ovarian cancer. Soon patients will be enrolled on to the trial which is testing a novel triplet of Keytruda (pembrolizumab), intravenous Avastin (bevacizumab) and oral low-dose Cytoxan (cyclophosphamide).

In an interview with CURE, Emese Zsiros, M.D., Ph.D., F.A.C.O.G., assistant professor of oncology in the Department of Gynecologic Oncology AND the Center for Immunotherapy at Roswell Park Cancer Institute, discussed the trial, as well as what role microbiomes play in the response patients have to immunotherapy agents.

Can you give a brief overview of your study and what you hope to find?

This is a new phase 2 clinical trial that enrolls patients who have recurrent ovarian cancer, epithelial ovarian cancer and fallopian tube cancer, which is all in the same category of disease. And during this study, we give them a drug combination of Keytruda, an immune checkpoint inhibitor produced by Merck. It's a combination with IV Avastin and oral low-dose Cytoxan.
The IV Avastin and the oral cyclophosphamide is somewhat the standard of care and accepted second line treatment for patients with recurrent ovarian cancer. But the addition of Keytruda has not been tried before. So this trial will enroll a total of 40 patients with recurrent ovarian cancer. Our main objective is to take a look at any improvement in PFS and also to look at toxicities to make sure that the combination of these three drugs is safe. 

Do you have a prediction of what kind of toxicities you may see?

Keytruda is a checkpoint inhibitor, so by its nature, it activates the immune system. As a result of that, there are some patients who experience autoimmune reactions. Most of the time these reactions are very mild and easily reversed by discontinuing the medication. The major autoimmune reactions that were seen in prior studies were reactions against the lungs or colon, so pneumonitis or colitis. Some patients have issues with thyroid disorders-- either hyperthyroidism or hypothyroidism -- hepatitis, and very rarely diabetes. Again, these reactions are very rare and most of the time they're very mild. By discontinuing the drug or potentially giving steroids, you can reverse these immune-related adverse events. 
As far as the Avastin, it's a monoclonal antibody. When you give this drug to patients, it has a very unique toxicity that comes from this drugs. But again, this is usually a very well-tolerated drug, but the side effects would be potential high blood pressure, wound-healing complications or some issues with kidneys, like creating more protein in the kidneys. Again, these side effects are typically really mild and by discontinuing the drug are reversible. 
With the oral Cytoxan, we don't really expect to have any major drug toxicities. With the combination of these three drugs, we're not really sure, but hopefully we will not see any additional toxicities. 

Where are you with the study now? Are you still enrolling patients?

We have opened our trial in the beginning of September and have enrolled our first five patients. Per our protocol, we enrolled five patients and they all have to go through three cycles to make sure that there are no major toxicities with this triple-drug combination. Some of them are just getting to the end of the third cycles and have seen no significant toxicities. 

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